In-vitro and in-vivo evaluation of ciprofloxacin liposomes for pulmonary administration

Objective: The aim of this study was to investigate the ciprofloxacin liposome of high encapsulation efficiency with optimal physical properties for pulmonary administration and to test its in-vivo potential in rats.

Methods: Ciprofloxacin-loaded liposome was prepared by gradient of ammonium sulfate method. The particle size and morphology were determined using a NANOPHOX particle size analyzer and a transmission electron microscope, respectively. Encapsulation efficiency was calculated by UV spectrophotometry. Ciprofloxacin liposome released in vitro was performed using simulated lung fluid. In-vivo studies, pharmacokinetics and pulmonary distribution, HPLC method was established to determine the concentration of ciprofloxacin in rat plasma and lung tissue. The pulmonary pathological section was used to observe the change of pulmonary pathology.

Results: The optimized ciprofloxacin liposome, which had a high encapsulation efficiency of 93.96%, and an average particle size of 349.6?nm with a span of 0.42, showed sustained in-vitro release. The optimized ciprofloxacin liposome was further examined in the in-vivo study in rats. The concentration of ciprofloxacin in lung and blood was simultaneously determined in each rat. The ratio of the AUC_lung value between ciprofloxacin liposome and ciprofloxacin solution was 288.33, whereas the relative bioavailability was 72.42%, and the drug targeting efficiency of ciprofloxacin liposome and ciprofloxacin solution by intratracheal administration were 799.71 and 2.01, respectively.

Conclusion: Ciprofloxacin liposome for pulmonary administration offered an attractive alternative that was able to deliver high concentrations of antibiotic directly to the chosen target site while minimizing the local irritation.     

Adhesive Backing Foil Interactions Affecting the Elasticity,Adhesion Strength of Laminates,and How to Interpret These Properties of Branded Transdermal Patches

ABSTRACT

Standard tensile strength and peel adhesion tests were carried out to investigate interactions of pressure-sensitive adhesives (PSAs) with several backing foils used for transdermal patches. Seven branded transdermal patches (Alora®, Cutanum®, Estraderm MX® 50, Estraderm TTS® 50, Fem7®-50 μg, Menorest®, Oesclim®) were included in the investigation. Their skin adhesion measured in several clinical trials was compared with the results of the laboratory measurements according to PSTC-1 (Peel Adhesion for Single Coated Tapes 180° Angle, Pressure Sensitive Tape Council, Illinois, 1996), such as Young's modulus at 3% elongation and peel adhesion to stainless steel. Data obtained for the PSA-coated backings (laminates) show increasing elasticity with increasing PSA thickness. Interactions of PSAs with backing foil became evident in significant changes in Young's modulus by low PSA thickness, as seen for the silicone adhesive. The Young's moduli of the laminates were found to be influenced not only by the elasticity of the backing foil but also by the chemical structure of the PSA. There was no correlation between the elasticity and peel adhesion of both the laminates and the branded patches. Likewise, for the branded patches the peel adhesion to stainless steel does not correlate with skin adhesion values obtained from clinical trials.

The Young's modulus of the branded patches was between 4 N/mm² (Oesclim®) and 501 N/mm² (Fem7®). For the branded transdermal patches no correlation was found between Young's modulus and both the peel force on stainless steel and the skin adhesion reported in studies.     

纳米银整理抗菌织物耐洗性及皮肤刺激性的评价

为考察抗菌织物的耐洗性及皮肤刺激性,以经纳米银整理的抗菌丝织物为实验对象,采用琼脂平皿扩散法和吸收法对其抗菌性能进行定性和定量实验,采用电感耦合等离子体质谱仪(ICP-MS)测定样品的金属溶出量,同时利用EPI-MODEL人体皮肤模型,对织物水萃取液的皮肤刺激性进行初步研究。结果显示:在洗涤50次后,样品对大肠杆菌8099和金黄色葡萄球菌ATCC6538的抗菌率依然在99%以上,具有良好的耐洗性能;织物水萃取液对皮肤无刺激性,较为安全。     

Acute effects of Aspergillus versicolor aerosols on murine airways

Mice were exposed to aerosols from Aspergillus versicolor extract by inhalation (for 15-20 min). Changes in respiratory function parameters were monitored during the exposure to evaluate acute effects on the upper and lower respiratory tracts and the conductive airways. The single inhalation exposure to A. versicolor aerosols at the range of 12-151 mg/m3 provoked upper respiratory tract irritation in the airways of mice. The higher the exposure concentration the higher was the increase in the sensory irritation (SI) response. No bronchoconstriction or pulmonary irritation was observed. The causative agents for the SI response in the fungal extract are not known.     

Substantivity of sunscreens—preparation and evaluation of some quaternary ammonium benzophenone derivatives

In continuation of previous studies on keratin-substantive sunscreens, two series of quaternary ammonium compounds, derived from 2,4-dihydroxy and from 4-hydroxybenzophenone and containing O-alkyl and N-alkyl chains of different length were prepared and submitted to substantivity tests on wool, to microbiological tests on two bacterial and two fungal species, and to tests for allergenicity/irritation on human skin. All compounds were rapidly adsorbed by wool in aqueous solution: as expected, the maximum amounts adsorbed at equilibrium (S_max), indicative of the skin substantivity, were greatest for the C12 N-alkyl derivatives, and showed a progressive decrease with increasing length of the N-alkyl substituent. No substantial substantivity differences were detected in four C12 quaternary derivatives, differing by the presence (or absence) of a 2-OH group in the benzophenone moiety and by the length of the O-alkyl ( n = 2 or 3) side chain. When tested for antimicrobial activity, however, only the 4-hydroxybenzophenone C12 quaternary derivatives showed an order of activity comparable with that of two reference compounds. The conditions leading to a maximal antibacterial activity in the present compounds appeared to be the absence of the 2-OH group, and a shorter O-alkyl side chain. None of the new quaternary derivatives showed skin-irritant properties. The results of this investigation, while confirming the peak substantivity of C12 quaternary derivatives, indicate the possibility of dissociating, in a quaternary ammonium sunscreen, the skin substantivity from other unwanted side-effects, and offer some guidelines for the development of safer agents of this type.     

微波辐射丙烯酸酯乳液聚合动力学研究

利用Discover微波精确有机合成系统,以甲基丙烯酸甲酯(MMA)、丙烯酸丁酯(BA)为聚合单体、过硫酸钾(KPS)为引发剂、十二烷基硫酸钠(SDS)为乳化剂进行乳液聚合。考察了微波辐射功率对乳液聚合反应的影响,分别考察了引发剂的质量,乳化剂质量,甲基丙烯酸甲酯质量,丙烯酸丁酯质量及反应温度,还对微波聚合反应动力学方程进行了研究。利用热重分析仪,差示扫描量热仪和傅立叶变换红外光谱仪对聚合物乳液的性能进行了测试与结构表征。实验结果表明,反应体系选择60 W为微波辐射条件,m(KPS)为0.06 g、m(SDS)为0.27 g、m(MMA)和m(BA)均为3 g,反应温度为343 K,测得聚合反应的活化能Ea=96.957 1 kJ/mol,建立了单模聚焦微波辐射乳液聚合的动力学方程:Rp=k[n(KPS)]1.107 9[n(SDS)]0.616 4[n(MMA)]1.205 9[n(BA)]-0.228。     

Surface and aqueous properties of anionic gemini surfactants having dialkyl amide,carboxyl, and carboxylate groups

A systematic study of the equilibrium surface properties (in water and in the presence of 10⁻² M NaCl) of a novel series of anionic gemini surfactants, (CH₂)₂[N(COC_nH_2n+1)CH(COOH)CH₂COOH]·2NaOH (GA), where (n+1)=8, 10, 12, 14, and 16, was investigated. The responses of humans to closed patch tests with (CH₂)₂[N(COC₁₁H₂₃)CH(COOH)−CH₂COOH]₂·2NaOH (GA-12) were also investigated. Premicellar self-aggregation (both in water and 10⁻² M NaCl) occurred when the N-acyl group contained more than 14 carbon atoms, since the critical micelle concentration (CMC) values decreased and the pC₂₀ values increased as (n+1) increased for (n+1) ≤14; the CMC values increased and the pC ₂₀ values decreased as (n+1) increased for (n+1)>14, both in water and in 10⁻² M NaCl. The absence of a break in the specific conductance-surfactant molar concentration plots for the GA homologs indicates protonation of the carboxylate group and strong Na⁺ release during micellization. This is a structural characteristic of the anionic geminis having N-dialkylamide and carboxylate groups in a molecule. The skin irritation potential of GA-12 is lower than that of the corresponding “monomer”, C₁₁H₂₃CON(CH₃)CH(COOH)CH₂(COOH)·NaOH, and the analog, C₁₁H₂₃CON(CH₃)CH₂COONa·H₂O.     

新型第二代丙烯酸酯结构胶

介绍了低臭味,低毒性,低刺激性及晾置时间较长的第二代丙烯酸酯结构胶（ＳＧＡ）的制备方法,讨论了丙烯酸酯类单体,氧化剂／还原剂及阻聚剂等原料品种及加入量对胶粘剂性能的影响。     

Exposure of eyes to perfume: a double-blind, placebo-controlled experiment

Environmental perfume exposure can elicit bothersome respiratory symptoms. Symptoms are induced at exposure levels which most people find tolerable, and the mechanisms are unclear. The aim of the study was to investigate patients with eye and respiratory symptoms related to environmental perfume, by exposing the eyes to perfume in a double-blind, placebo-controlled study.Twenty-one eczema patients with respiratory symptoms elicited by perfume were compared with 21 healthy volunteers in a sex- and age-matched case-control study. The participants completed a symptom questionnaire, and underwent a double-blind, placebo-controlled exposure to perfume. Of the 42 individuals tested, 10 had more eye symptoms (irritation, itching, and tears) during perfume exposure than during placebo exposures, and eight of these individuals (P = 0.07, Fisher's exact test) belonged to the patient group. A true positive eye reaction to perfume was significantly associated with identification of perfume as an active exposure (P < 0.05). In this study, vapor of perfume elicited irritation in the eyes independently of olfaction, but the relative importance of ocular chemoperception in relation to elicitation of respiratory symptoms from common environmental exposures to perfume remains unclear. We investigated the hypothesis of an association between respiratory symptoms related to perfume and ocular perfume sensitivity by exposing the eyes to perfume in a double blind, placebo-controlled experiment. Vapors of perfume provoked symptoms in the relevant eye in some patients and healthy control persons, but under our exposure conditions, ocular chemesthesis failed to elicit respiratory symptoms.     

Organic compounds in office environments - sensory irritation, odor, measurements and the role of reactive chemistry

Abstract Sensory irritation and odor effects of organic compounds in indoor environments are reviewed. It is proposed to subdivide volatile organic compounds (VOCs) into four categories: (i) chemically non-reactive, (ii) chemically 'reactive', (iii) biologically reactive (i.e. form chemical bonds to receptor sites in mucous membranes) and (iv) toxic compounds. Chemically non-reactive VOCs are considered non-irritants at typical indoor air levels. However, compounds with low odor thresholds contribute to the overall perception of the indoor air quality. Reported sensory irritation may be the result of odor annoyance. It appears that odor thresholds for many VOCs probably are considerably lower than previously reported. This explains why many building materials persistently are perceived as odorous, although the concentrations of the detected organic compounds are close to or below their reported odor thresholds. Ozone reacts with certain alkenes to form a gas and aerosol phase of oxidation products, some of which are sensory irritants. However, all of the sensory irritating species have not yet been identified and whether the secondary aerosols (ultrafine and fine particles) contribute to sensory irritation requires investigation. Low relative humidity may exacerbate the sensory irritation impact. Practical Implications Certain odors, in addition to odor annoyance, may result in psychological effects and distraction from work. Some building materials continually cause perceivable odors, because the odor thresholds of the emitted compounds are low. Some oxidation products of alkenes (e.g. terpenes) may contribute to eye and airway symptoms under certain conditions and low relative humidity.